Detection Of Haplosporidium-nelsoni (Haplosporidia, Haplosporidiidae) In Oysters By PCR Amplification

Haplosporidium nelsoni is a protistan pathogen of the eastern oyster Crassostrea virginica, and has contributed to the decline of the oyster population in the Chesapeake Bay. From comparison of the sequence data of the 16S-like rDNA of H. nelsoni with those of Minchinia teredinis and other related organisms, 2 oligonucleotides which were specific to H. nelsoni and suitable for use as PCR primers were identified. These primers amplified a 564 base pair fragment of the small subunit (SSU) rRNA gene of H. nelsoni, but did not amplify genomic oyster DNA or the SSU rRNA genes of the haplosporidians Haplosporidium costale, Haplosporidium louisiana, or M. teredinis. The PCR primers were able to detect the H. nelsoni SSU rDNA from 50 ng of infected oyster genomic DNA or from 10 fg of cloned H. nelsoni SSU rDNA. The ability of the PCR primers to diagnose H. nelsoni-infected oysters was compared to the established techniques of hemolymph settlement analysis in Farley chambers and histological examination from a sample of 20 oysters. Hemolymph settlement analysis detected infection in 10 oysters and histology revealed infections in 11 oysters. PCR amplification of DNA from hemolymph initially detected infections in 15 oysters and reamplification of the PCR products detected an additional 4 infections. PCR amplification is a more sensitive diagnostic assay for H. nelsoni than traditional techniques

Application of a spatially-weighted Relief algorithm for ranking genetic predictors of disease

Background: Identification of genetic variants that are associated with disease is an important goal in elucidating the genetic causes of diseases. The genetic patterns that are associated with common diseases are complex and may involve multiple interacting genetic variants. The Relief family of algorithms is a powerful tool for efficiently identifying genetic variants that are associated with disease, even if the variants have nonlinear interactions without significant main effects. Many variations of Relief have been developed over the past two decades and several of them have been applied to single nucleotide polymorphism (SNP) data. Results: We developed a new spatially weighted variation of Relief called Sigmoid Weighted ReliefF Star (SWRF*), and applied it to synthetic SNP data. When compared to ReliefF and SURF*, which are two algorithms that have been applied to SNP data for identifying interactions, SWRF* had significantly greater power. Furthermore, we developed a framework called the Modular Relief Framework (MoRF) that can be used to develop novel variations of the Relief algorithm, and we used MoRF to develop the SWRF* algorithm. Conclusions: MoRF allows easy development of new Relief algorithms by specifying different interchangeable functions for the component terms. Using MORF, we developed a new Relief algorithm called SWRF* that had greater ability to identify interacting genetic variants in synthetic data compared to existing Relief algorithms. © 2012 Stokes and Visweswaran.; licensee BioMed Central Ltd

The application of network label propagation to rank biomarkers in genome-wide Alzheimer's data

Background: Ranking and identifying biomarkers that are associated with disease from genome-wide measurements holds significant promise for understanding the genetic basis of common diseases. The large number of single nucleotide polymorphisms (SNPs) in genome-wide studies (GWAS), however, makes this task computationally challenging when the ranking is to be done in a multivariate fashion. This paper evaluates the performance of a multivariate graph-based method called label propagation (LP) that efficiently ranks SNPs in genome-wide data.Results: The performance of LP was evaluated on a synthetic dataset and two late onset Alzheimer's disease (LOAD) genome-wide datasets, and the performance was compared to that of three control methods. The control methods included chi squared, which is a commonly used univariate method, as well as a Relief method called SWRF and a sparse logistic regression (SLR) method, which are both multivariate ranking methods. Performance was measured by evaluating the top-ranked SNPs in terms of classification performance, reproducibility between the two datasets, and prior evidence of being associated with LOAD.On the synthetic data LP performed comparably to the control methods. On GWAS data, LP performed significantly better than chi squared and SWRF in classification performance in the range from 10 to 1000 top-ranked SNPs for both datasets, and not significantly different from SLR. LP also had greater ranking reproducibility than chi squared, SWRF, and SLR. Among the 25 top-ranked SNPs that were identified by LP, there were 14 SNPs in one dataset that had evidence in the literature of being associated with LOAD, and 10 SNPs in the other, which was higher than for the other methods.Conclusion: LP performed considerably better in ranking SNPs in two high-dimensional genome-wide datasets when compared to three control methods. It had better performance in the evaluation measures we used, and is computationally efficient to be applied practically to data from genome-wide studies. These results provide support for including LP in the methods that are used to rank SNPs in genome-wide datasets. © 2014 Stokes et al.; licensee BioMed Central Ltd

Effect of Reimbursement Reductions on Bone Mineral Density Testing for Female Medicare Beneficiaries

Abstract Background: We examined whether the recent reimbursement reductions on the bone mineral density (BMD) test affected BMD testing in female Medicare beneficiaries with or without supplemental private health insurance. Methods: Retrospectively analyzing hospital administrative and clinical data on female Medicare beneficiaries (n=1320), we reviewed whether participants received BMD testing before (January 2004?December 2006) or after (January 2007?December 2009) reimbursement reductions for BMD testing. After adjusting for demographics and clinical characteristics, we performed Cox proportional hazard regression analyses of the BMD test including data from all study participants; we then performed separate regression analyses using data with or without supplemental private health insurance. Results: In those without supplemental private health insurance (n=421), less frequent BMD testing occurred after reimbursement reductions for BMD testing (hazard ratio [HR] 0.67, 95% confidence intervals [CI] 0.34-0.98; p=0.03). By contrast, in the overall participants (n=1320) and those with supplemental private health insurance (n=899), the number of BMD tests did not change significantly after reimbursement reductions for BMD testing. Conclusions: We found a significant association between reimbursement reductions and decrease in BMD tests in female Medicare beneficiaries without supplemental private health insurance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98463/1/jwh%2E2012%2E3517.pd

Defining the Differences Between Episodic Migraine and Chronic Migraine

Chronic migraine (CM) and episodic migraine (EM) are part of the spectrum of migraine disorders, but they are distinct clinical entities. Population-based studies have shown that those with CM demonstrate higher individual and societal burden because they are significantly more disabled than those with EM and have greater impaired quality of life both inside and outside the home. Proper diagnosis of both conditions requires clearly defined clinical criteria. Diagnosis enables the initiation of appropriate treatments and risk-factor modification, which ultimately improve functional status and quality of life for persons with migraine. Recognizing that both disorders are on the spectrum of migraine, this review serves as a guide to define the disease state of CM as distinct from EM in terms of clinical, epidemiological, sociodemographic, and comorbidity profiles

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

The prevalence of hand and wrist osteoarthritis in elite former cricket and rugby union players

OBJECTIVES: This study aimed to determine the prevalence of hand and wrist osteoarthritis in former elite cricket and rugby union players, by sport and playing position, and to define the prevalence of severe hand injury, and its association with hand osteoarthritis. DESIGN: Cross-sectional. METHODS: Data from cross-sectional studies of former elite male cricket and rugby players were used to determine the prevalence of hand pain, physician-diagnosed osteoarthritis, and previous severe injury. Multivariable logistic regression was used to determine the association of previous injury with pain and osteoarthritis. RESULTS: Data from 200 cricketers and 229 rugby players were available. Complete case analysis resulted in 127 cricketers and 140 rugby players. Hand pain was more prevalent amongst cricketers (19.7%) than rugby players (10.0%). The prevalence did not differ between cricket and rugby players for hand osteoarthritis (2.4% and 3.6%), wrist osteoarthritis (1.6% and 2.1%), or previous severe hand injury (36.2% and 31.4%). No significant association between previous hand injury and pain or osteoarthritis was identified in either sport. CONCLUSIONS: Former elite cricketers reported more hand pain than rugby players. No significant association was found between self-reported severe injury and hand osteoarthritis in either cohort, potentially indicating that risk factors aside from injury may be more prominent in the development of hand osteoarthritis

Structural and micro-anatomical changes in vertebrae associated with idiopathic-type spinal curvature in the curveback guppy model

Background: The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature thatdevelops during growth. Prior work has revealed several important developmental similarities to the human idiopathicscoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that areassociated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a femalebias for severe curve magnitudes in the population.Methods: Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males andfemales. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variancetested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature,sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize microarchitecturalchanges in affected vertebrae and the intervertebral region.Results: In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion,migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexualdimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than domales. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reducedwidth at the middle of their vertebrae, relative to males.Conclusions: Based on similarities to human spinal curvatures and to animals with induced curves, the concaveconvexbiases described in the guppy suggest that there is a mechanical component to curve pathogenesis incurveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similarto Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanicalcomparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature incurveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics.Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the femalebias for severe curves that is observed in the population